P72 Development of a novel platform trial evaluating systemic therapies in adult atopic eczema with parallel mechanistic studies (BEACON and BEACONomics): a UK-wide interdisciplinary collaboration

Abstract

Abstract Atopic eczema is common and profoundly impacts on the quality of life, and psychological and social function. More severe disease often requires systemic (standard or targeted) immune-modifying therapy; however, drug response and tolerability vary in practice. As the molecular effects of the drugs used have not been characterized in detail, the causes of such variability remain poorly understood. There remains equipoise as to which drug is best, with no active comparator data for standard vs. targeted therapies. We have designed a global first trial in atopic eczema to directly compare the effectiveness and tolerability of standard and targeted drugs. The platform design, building on expertise in cancer and COVID (Medical Research Council Clinical Trials Unit), allows incorporation of additional comparator arms as new treatments emerge. We used multistakeholder input from patients [partnership with National Eczema Society, patient coapplicants, national patient survey (> 90 participants), public and patient involvement webinar feedback], clinicians [UK Dermatology Clinical Trials Network, national surveys (> 50 clinicians)], health economics and qualitative researchers. We partnered with experts in skin biology and single-cell methods, exploiting high-throughput analytic pipelines of the Human Cell Atlas, to design embedded studies to dissect mechanisms underlying drug effects. The trial (BEACON), which commenced in February 2023, is funded through the NIHR Health Technology Assessment programme. This 12-month multiarm trial involves > 400 adults with moderate-to-severe eczema requiring systemic therapy from > 30 UK sites. It is designed around real-world practice and incorporates inclusive recruitment strategies and remote data capture. BEACON will establish the comparative clinical effectiveness, tolerability and cost-effectiveness of methotrexate, ciclosporin and dupilumab. It will transition to a multiarm, multistage platform trial, enabling additional treatment arms. The primary outcome is EASI at 6 months, with key Harmonising Outcome Measures for Eczema outcome measures incorporated. Dose increases and treatment switching (6 months) are possible, mirroring standard practice. BEACON-omics is funded through the National Institute for Health and Care Research Efficacy and Mechanism Evaluation and Open Targets (public–private partnership). This longitudinal cohort study will profile serial skin and blood samples at scale (150 participants) using single-cell multiome and spatial transcriptome approaches, to investigate mechanisms of treatment effects and provide a foundational resource for new target discovery. This world-first platform trial for systemic therapies in adult atopic eczema, and one of the first in chronic inflammatory disease, will provide comparative data on commonly used systemic treatments and incorporate novel therapies as they emerge. Integrated cutting-edge discovery science will maximize the potential of the platform.